Synchronization of the nucleus accumbens-ventral hippocampus reflects cooperative ability and predicts social dysfunction after training in mice

Abstract Cooperation is a fundamental form of social behavior that promotes collective benefits and group survival. Although considerable progress has been made in understanding cooperation from behavioral and theoretical perspectives, the neural activities underlying cooperative behavior remain incompletely understood. In the present study, we established a cooperative behavioral paradigm in pairs of mice using a Skinner box, with the protocol spanning 22 days. Mice were retrospectively classified into high-, middle-, and low-performance groups based on their performance in the cooperation task. In vivo local field potential recordings from the nucleus accumbens and ventral hippocampus were then conducted in the three groups. High-cooperation mice showed significantly increased delta and low-gamma power in the nucleus accumbens, as well as enhanced delta, theta, beta, and low-gamma power in the ventral hippocampus, compared to low-cooperation mice. Meanwhile, nucleus accumbens–ventral hippocampus coherence within the beta and low-gamma frequency bands was significantly reduced in high-cooperation animals. Behaviorally, high-cooperation mice exhibited social dysfunction as shown by reduced social interaction and more pronounced anxiety-like behaviors compared with low-cooperation mice after training. Collectively, these findings provide early evidence that individual differences in cooperative behavior are associated with distinct patterns of neural oscillatory activity within the nucleus accumbens–ventral hippocampus circuit. Moreover, enhanced cooperative performance was correlated with alterations in social and affective behavior, such as increased social avoidance and anxiety-like behavior. The results suggest that nucleus accumbens–ventral hippocampus oscillatory dynamics may represent a neural correlate of cooperative behavior, and that training-induced differences in cooperative performance are associated with subsequent changes in social and affective functioning.